Role of the cytoskeleton in axonal growth during motor neurones development and regeneration in Xenopus

Spinal cord injury in humans causes severe disabilities such as paralysis because the neural tissue does not regenerate. Furthermore, degeneration of motor neurones leads to diseases such as Amyotrophic lateral sclerosis (ALS) with devastating consequences. In contrast, Xenopus laevis tadpoles can fully regenerate their tails after amputation, including tissues also present in humans such as skeletal muscles, the vasculature and the spinal cord. However, the molecular and cellular mechanisms of tail regeneration are still poorly understood.

In the laboratory, we are particularly interested in the molecular mechanisms regulating neuronal growth and shape (or morphology) in the complex environment of the whole organism. In particular, we are investigating how motor neurones develop, function and regenerate. Motor neurons are highly specialised cells with long axons, which can travel up to one metre away from their cell body to reach and innervate their target organs, the muscles. Therefore, the growth, guidance and morphology of these axons must be tightly controlled

To achieve these objectives, we will study the mechanisms regulating the dynamic of the actin and microtubule cytoskeleton during axonal growth and regeneration in Xenopus motor neurones. To this end, transgenic lines expressing fluorescent proteins labelling the different components of the cytoskeleton specifically in motor neurones will be generated. We will use these transgenic lines to uncover the molecular mechanisms regulating cytoskeleton dynamics in neurons during embryonic development and regeneration. The outcome of this work will have significant implications for neuronal regenerative research and motor neurones diseases.

Techniques used for this project: in vivo live imaging / generation of transgenic Xenopus lines / generation of Xenopus knock-out lines using TALENs technology / molecular biology / immunofluorescence.